tert-Butanol → HCID 131732418, compound

HRID 1843923Notes

Reaction equation

HRID 1843923 reaction equation
CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.C[C:36]([OH:39])([CH3:38])C.C([O-])([O-])=[O:41].[K+].[K+].Cl[C:47]1[C:48]([F:65])=[CH:49][CH:50]=[C:51]2[C:56]=1[C:55](=[O:57])[N:54]([C:58]1[CH:59]=[N:60][CH:61]=[CH:62][C:63]=1[CH3:64])[CH2:53][CH2:52]2.[CH:66]1([CH2:69][NH2:70])[CH2:68][CH2:67]1>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C(OC(=O)C)C.O>[C:36]([OH:39])(=[O:41])[CH3:38].[CH:66]1([CH2:69][NH:70][C:47]2[C:48]([F:65])=[CH:49][CH:50]=[C:51]3[C:56]=2[C:55](=[O:57])[N:54]([C:58]2[CH:59]=[N:60][CH:61]=[CH:62][C:63]=2[CH3:64])[CH2:53][CH2:52]3)[CH2:68][CH2:67]1

Participants

9

Reactant 5

HCID 6386tert-ButanolHCID 11430Potassium CarbonateHCID 75646CyclopropanemethanamineHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 56942894HCID 56942894, compound

Product 1

HCID 131732418HCID 131732418, compoundYield 10.72%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

Palladium acetate (0.58 mg, 0.0025 mmol), X-Phos (3.69 g, 0.0077 mmol), t-BuOH (0.66 g, 0.005 mol) and water were taken in a sealed tube under argon atmosphere. The reaction mixture was heated to 80° C. for 1 minute. This was followed by the addition of K2CO3 (49.9 mg, 0.3620 mmol), 8-chloro-7-fluoro-2-(4-methyl-pyridin-3-yl)-3,4-dihydro-2H-isoquinolin-1-one (34A: 75 mg, 0.2586 mmol) and C-cyclopropyl-methylamine (22 mg, 0.3103 mmol) under argon atmosphere. The resulting mixture was refluxed at 110° C. for 1 hour. The reaction was monitored by TLC (100% ethylacetate). The reaction mixture was partitioned between water and ethylacetate. The organic layer was washed with brine solution, dried over Na2SO4 and concentrated. Purification by column chromatography on silica gel (50% ethylacetate in hexane), followed by preparative HPLC afforded 9 mg of the product (10.72% yield).

Workup

  1. temperatureThe resulting mixture was refluxed at 110° C. for 1 hour
  2. customThe reaction mixture was partitioned between water and ethylacetate
  3. washThe organic layer was washed with brine solution
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated
  6. customPurification by column chromatography on silica gel (50% ethylacetate in hexane)

Sources & evidence

ORD record
ord-49671f88416b41f096fe74a835fd30cb
Source dataset
uspto-grants-2015_02
Patent number
US08946260B2

Reaction notes

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